Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk

Recently, ARLTS1 (ADP-ribosylation factor-like tumor suppressor gene 1) has been identified as a tumor suppressor gene, playing a major role in apoptotic signaling. The ARLTS1 Trp149Stop mutation has been shown to predispose to general familial cancer and high-risk familial breast cancer (BC), provoking the attenuation of apoptotic function. We studied the impact of the ARLTS1 Pro131Leu and Cys148Arg variants on high-risk familial and familial BC risk, investigating 482 familial BC cases (including 305 high-risk cases) and 530 control individuals. Unlike ARLTAS1 Pro131Leu, Cys148Arg revealed a significant association with an increased risk of high-risk familial BC (odds ratio (OR) = 1.47, 95% confidence interval (95% CI) = 1.04-2.06, p = 0.03) in a dose-dependent manner (P-trend = 0.007). The genotype distribution of Cys148Arg in familial cases was similar, indicating Significance as well (OR = 1.48, 95% CI = 1.10-1.99, p = 0.009; P-trend = 0.003). On the basis of the small number of 46 cases, we additionally showed an association between the Trp149Stop mutation and an increased risk of bilateral BC (OR = 4.11, 95% CI = 1.27-13.31, p = 0.011). (c) 2005 Wiley-Liss, Inc.